Regulation of homologous recombination by RNF20-dependent H2B ubiquitination.

The E3 ubiquitin ligase RNF20 regulates chromatin structure by monoubiquitinating histone H2B in transcription. Here, we show that RNF20 is localized to double-stranded DNA breaks (DSBs) independently of H2AX and is required for the DSB-induced H2B ubiquitination. In addition, RNF20 is required for the methylation of H3K4 at DSBs and the recruitment of the chromatin-remodeling factor SNF2h. Depletion of RNF20, depletion of SNF2h, or expression of the H2B mutant lacking the ubiquitination site (K120R) compromises resection of DNA ends and recruitment of RAD51 and BRCA1. Consequently, cells lacking RNF20 or SNF2h and cells expressing H2B K120R exhibit pronounced defects in homologous recombination repair (HRR) and enhanced sensitivity to radiation. Finally, the function of RNF20 in HRR can be partially bypassed by forced chromatin relaxation. Thus, the RNF20-mediated H2B ubiquitination at DSBs plays a critical role in HRR through chromatin remodeling.

Nakamura K ，Kato A ，Kobayashi J ，Yanagihara H ，Sakamoto S ，Oliveira DV ，Shimada M ，Tauchi H ，Suzuki H ，Tashiro S ，Zou L ，Komatsu K ... -  《-》

Histone chaperone FACT regulates homologous recombination by chromatin remodeling through interaction with RNF20.

Oliveira DV ，Kato A ，Nakamura K ，Ikura T ，Okada M ，Kobayashi J ，Yanagihara H ，Saito Y ，Tauchi H ，Komatsu K ... -  《-》

H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation.

Meiotic recombination is essential for fertility in most sexually reproducing species, but the molecular mechanisms underlying this process remain poorly understood in mammals. Here, we show that RNF20-mediated H2B ubiquitination is required for meiotic recombination. A germ cell-specific knockout of the H2B ubiquitination E3 ligase RNF20 results in complete male infertility. The Stra8-Rnf20-/- spermatocytes arrest at the pachytene stage because of impaired programmed double-strand break (DSB) repair. Further investigations reveal that the depletion of RNF20 in the germ cells affects chromatin relaxation, thus preventing programmed DSB repair factors from being recruited to proper positions on the chromatin. The gametogenetic defects of the H2B ubiquitination deficient cells could be partially rescued by forced chromatin relaxation. Taken together, our results demonstrate that RNF20/Bre1p-mediated H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation, and suggest an old drug may provide a new way to treat some oligo- or azoospermia patients with chromatin relaxation disorders.

Xu Z ，Song Z ，Li G ，Tu H ，Liu W ，Liu Y ，Wang P ，Wang Y ，Cui X ，Liu C ，Shang Y ，de Rooij DG ，Gao F ，Li W ... -  《-》

The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression.

Shema E ，Tirosh I ，Aylon Y ，Huang J ，Ye C ，Moskovits N ，Raver-Shapira N ，Minsky N ，Pirngruber J ，Tarcic G ，Hublarova P ，Moyal L ，Gana-Weisz M ，Shiloh Y ，Yarden Y ，Johnsen SA ，Vojtesek B ，Berger SL ，Oren M ... -  《-》

E3 Ubiquitin Ligases RNF20 and RNF40 Are Required for Double-Stranded Break (DSB) Repair: Evidence for Monoubiquitination of Histone H2B Lysine 120 as a Novel Axis of DSB Signaling and Repair.

Histone posttranslational modifications play fundamental roles in the regulation of double-stranded DNA break (DSB) repair. RNF20/RNF40-mediated monoubiquitination of histone H2B on lysine 120 (H2Bub) has been suggested as a potential mediator of DSB repair, although the nature and function of this posttranslational modification remain enigmatic. In this report, we demonstrate that RNF20 and RNF40 are required for DSB repair leading to homologous recombination (HR) and class switch recombination, a process driven by nonhomologous end joining (NHEJ), in mouse B cells. These findings suggest a role for RNF20 and RNF40 in DSB repair proximal to NHEJ/HR pathway choice and likely in the signaling of DSBs. We found that DSBs led to a global increase in H2Bub but not the transcription-associated posttranslational modifications H3K4me3 and H3K79me2. We also found that H2AX phosphorylation was dispensable for H2Bub and that ATM and ATR jointly regulate ionizing radiation (IR)-induced H2Bub. Together, our results suggest that RNF20, RNF40, and H2Bub may represent a novel pathway for DSB sensing and repair.

So CC ，Ramachandran S ，Martin A 《-》